The overall objectives of this grant are to investigate the cerebral vasculature, in particular, its regulation by vasocontrictor and vasodilator nerves and its reactivity to drugs. The detailed mechansims whereby these nerves regulate vascular tone differ from other regional vascular beds. For example, the alpha-receptor on the cerebral vascular smooth muscle reacts in a different way to alpha agonists; the nature of the response elicited by the drug differs in that in low concentrations the response is only transient and in higher concentrations it is maintained. The transmitter released from the vasodilator nerves has not been established; although several lines of evidence suggest that it is cholinergic, others do not confirm. In order to resolve this problem, choline acetyltransferase activity has been assessed in cerebral blood vessels. The high concentration found in these vessels is the strongest evidence to date that the acetylcholine is the transmitter. Experiments will be conducted to further elucidate the unique matters of these neurogenic control mechanism.